The Mississippian peoples were hierarchical mound builders who occupied much of the eastern part of North America between 700 and 1550. Connected culturally and technologically, these eastern Woodland Native Americans lived along the Mississippi River, on its tributaries, and in the riverine basins along the Gulf of Mexico and Atlantic Oceans. Their domain stretched from Florida through the Appalachian Mountains and extended to the eastern part of the Great Plains.

Although early Spanish conquistadors, such as Hernando de Soto and others, left descriptions of the Mississippians as they existed at the end of the era, archaeology provides most of what we know about these cultures. The Spanish and archaeological sources both describe densely populated centers in the Mississippian era. Population estimates vary, but the Mississippians probably numbered in the millions.

The intense cultivation of maize enabled Native Americans to produce the surpluses necessary to support the growing populations and political hierarchy. Although men continued to hunt and women still gathered nuts and fruits, the introduction of cleared-field corn agriculture in about 800 provided the means for the rise of large Mississippian chiefdoms. Women primarily controlled the fields in Mississippian society, and eventually their corn, beans, and squash provided most of the food.

The Mississippian chiefdoms spoke mutually unintelligible languages, competed for trade and hunting grounds, and waged wars of conquest with one another. Warfare was the norm in Mississippian society, providing both the means for territorial expansion and the threat of conquest. As the palisades at Cahokia attest, Mississippians lived with an omnipresent fear of invasion. Other evidence points to the esteem afforded to those warriors who proved themselves in battle. Other social and cultural similarities likewise connected the chiefdoms into a complex network of competing chiefdoms. They shared the technology that allowed shell-tempered pottery, lived in similar forms of circular housing, hunted with bow and arrows, used short-handled hoes made of stone or shells, and lived in hierarchical societies where chiefs from elite lineages received tribute. Trading networks also connected the chiefdoms, allowing elites to create goodwill with neighbors as well as to obtain the exotic goods required to maintain one's social and sacred position.

Mississippian societies also shared the Southeastern Ceremonial Complex. This artistic tradition contained a shared set of symbols and iconography that reveals aspects of the Mississippian cosmology and social structure. Many scholars assert that the paramount chiefs were believed to have had spiritual powers and were expected to use them to benefit their communities. Chiefs also were believed to have possessed a special relationship with the sun, perhaps explaining the construction of the mounds to bring them closer together.

Mound building was the most distinguishable characteristic of the Mississippian people. The mounds were usually pyramidical and most often (but not always) part of large urban centers. Cahokia, located in Illinois near today's St. Louis, Missouri, was the largest of these centers. Monk's Mounds was the largest of its mounds, measuring about 100 feet high and 1,000 feet in length. This rectangular mound had several flat tiers with sacred buildings on top. Cahokia had more than 100 other significantly smaller mounds across its two hundred acres. Mississippians built various public buildings and houses for their paramount chiefs and other elites on top of these mounds, while other mounds contained the graves for their leaders. The grave goods at this site contain items from as far away as the Great Lakes, Rocky Mountains, and Gulf of Mexico. At its height, wooden palisades surrounded Cahokia, and it served as the centerpiece of a theocratic chiefdom containing tens of thousands of residents. Cahokia collapsed by 1150, prior to the arrival of the Europeans, and other smaller chiefdoms took control of their territory. The other excavated mounds have tended to be smaller, but similarly the center of large concentrations of people. In total, the Mississippians built more than a thousand mounds in the United States.

Instability characterized the Mississippian era. Warfare and conquest created some instability, but the rise and fall of chiefdoms likely had more to do with the internal problem of succession. The death of paramount chiefs may have resulted in the renewed competition of different networks of kin to replace deceased leaders. Disagreements resulted in migrations and the splintering of communities. Even when a successor was found, the Mississippian structure remained fragile. If followers feared that their successor lacked the spiritual power to protect the community, some societies collapsed, while others simply became depopulated as a result of massive migrations. The arrival of the Europeans and their diseases in the sixteenth century brought disruptions that the Mississippian chiefdoms could not withstand.